PHARMACOLOGY A Class Act
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- Horace Sullivan
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1 PHARMACOLOGY A Class Act The arrival of a good clown exercises a more beneficial influence on the health of a town than 20 asses laden with drugs. Dr. Thomas Sydenham ( )
2 The Numbers 30 years ago there were 900 drugs to choose from in the PDR Today there are over 11,000
3 Don t PANIC. Know the 30 or 40 drugs you use daily in your clinical practice as well as the most common drugs most likely used by your patients (age and gender specific) Helpful hints
4 Generics vs. Brand names As a general rule, classes of drugs have the same generic last name Prils ACE inhibitors Sartans ARBs (angiotensin receptor blockers) Triptans treatment of acute migraine headache Statins Lower LDL-cholesterol Dipines calcium channel blockers Tidines H2 blockers reduce nighttime acid Prazoles Proton Pump Inhibitors, GERD Azoles antifungal
5 Prils The ACE inhibitors Captopril (Capoten) Enalapril (Vasotec) Lisinopril (Prinivil, Zestril) Perindopril (Aceon) Moxepril (Univasc) Benazepril (Lotensin) Quinapril (Accupril) Trandolapril (Mavik) Ramipril (Altace)
6 A little refresher on the kidney At any given moment, the kidney is sensing the pressure and volume of blood flow throughout the body Low volume or low BP, the kidney will release renin from a small area (the JGA) just inside the afferent arteriole Renin (the messenger) (liver) angiotensin 1 angiotensin 2 via Angiotensin Converting Enzyme (ACE) Angiotensin 2 triggers the release of AL from the adrenal cortex RENIN ANGIOTENSIN 2 ANGIOTENSIN 1
7 So, let s get back to the original story Who is ACE and why do we want to inhibit him? RENIN ANGIOTENSIN 1 ACE -- ALDOSTERONE ANGIOTENSIN 2
8 What does angie do? Tenses your angios vasoconstricts the arterioles and increases blood pressure Triggers release of AL aldosterone (from the adrenal cortex to save Na+ & H2O ( BP) and excrete K+ but that s not all ANGIOTENSIN 2 ALSO Increases inflammation in the arteries Prothrombotic Increases tissue resistance to insulin Potent growth factor remodels tissues
9 So, if you were an ACE inhibitor, what would you do? 1. Anti-hypertensive agent via vasodilation and inhibition of aldosterone (Na+ and H20 diuresis) 2. Treatment of heart failure by inhibiting renin-angiotensinaldosterone CHF is a HYPER-RENINEMIC state 3. Anti-inflammatory 4. Anti-thrombotic 5. Hypoglycemic (be careful when starting ACE inhibitors in diabetics) 6. Decrease growth of tissues or remodeling Is remodeling a good word? Hmmmmm.yes, in your
10 But NOT In your heart after a myocardial infarction, OR In your heart with chronic heart failure, OR In your blood vessels with hypertension, OR In your kidneys with diabetes Angie is a bad girl
11 To summarize ACE inhibitors are used for: Hypertension (*night time dosing of antihypertensive drugs dippers (10% night) vs. non-dippers ) (American Journal of Kidney Diseases December 2007) Decrease the remodeling of the heart in heart failure patients and post-mi patients (clearly beneficial in MI patients years of age, but not so clear in patients older than 75) Beneficial in patients with anterior ST-elevation MIs and in patients with MIs complicated by HF or significant LV systolic dysfunction with LV ejection fractions less than 40%
12 To summarize ACE inhibitors are used for: Decrease the risk of 1 st and 2 nd myocardial infarctions in high-risk patients due to antiinflammatory effects Stroke prevention Prevention of diabetic nephropathy Decrease insulin resistance and reduce the risk of progression to type 2 diabetes
13 Sartans --ARBs Angiotensin receptor blockers (bypass ACE) and work by blocking the angiotensin-2 receptors on tissues Who are they? The Sartan Sisters losartan Cozaar valsartan Diovan candesartan Atacand irbesartan Avapro telmisartan Micardis olmesartan Benicar eprosartan--tevetan
14 A new class of drugs Direct renin inhibitors (DRI) Aliskirin (Tekturna) Blocks the entire RAA system
15 Olols, alols, ilols Beta blockers acebutolol (Sectral) atenolol (Tenormin) betaxolol (Kerlone) bisoprolol (Zebeta) carvedilol (Coreg) (non selective, alpha-1 blocker)* Esmolol (Brevibloc) labetalol (Trandate)(Normodyne) safe during pregnancy metoprolol succinate* and tartrate (Toprol XL, Lopressor) {Betaloc}* (not tartrate for CHF) *EBM (evidence-based medicine) for heart failure to prevent remodeling of the heart
16 Beta-blockers, continued nadolol (Corgard) nebivolol (Bystolic) oxprenolol (Trasicor, Slow-Trasicor) penbutolol (Levatol) pindolol {Visken} propranolol (Inderal)(1968)(nonselective) timolol (Blocadren)
17 SNS receptors and actions B1 found on heart muscle; epinephrine binds to B1 and increases heart rate and strength of contraction (chronotropic and inotropic) B2 skeletal muscle (tremor), bronchioles of the lungs (bronchodilation), large arteries of the legs (vasodilation), piloerection (hairs stand up on back of neck and arms)
18 Same slide as last throw in beta and alpha blockers B1 found on heart muscle; epinephrine binds to B1 and increases heart rate and strength of contraction (chronotropic and inotropic) CARDIOSELECTIVE BETA BLOCKERS B2 skeletal muscle (tremor), bronchioles of the lungs (bronchodilation), large arteries of the legs (vasodilation), piloerection (hairs stand up on back of neck and arms) NONSELECTIVE BETA BLOCKERS
19 Why don t we pick just any old beta blocker? Because the non-cardioselective beta blockers block both the B1 AND B2 receptors and can wreak havoc in certain patient populations B2 blockade can cause bronchoconstriction and exacerbate COPD & asthma as well as vasoconstrict the femoral artery {exacerbate [peripheral artery disease} propranolol (Inderal), nadolol (Corgard), timolol (Blocadren), carvedilol (Coreg)
20 Olols, alols, ilols Cardioselective? (B1 receptors) if you block the B1 receptors on the heart, the heart rate and contractile state decrease cardiac output falls, heart rate falls (10-15%), blood pressure falls, workload of the heart decreases angina, SVT atenolol (Tenormin), metoprolol (Lopressor), betaxolol (Kerlone); bisoprolol (Zebeta), nebivolol doses <10 mg) *Beta Blockers are NO longer considered FIRST line therapy for essential hypertension (diuretics, ACE inhibitors**, ARBs, and CCBs are better choices)
21 Beta blockers other properties Water-soluble? (low lipophilicity) atenolol (Tenormin), nadolol (Corgard), labetalol (Trandate), nebivolol (Bystolic) Lipid-soluble? (high lipophilicity--cross the blood brain barrier) CNS side effects anhedonia (the Blahs ) BUT the lipid-soluble can also calm down the brain propranolol (Inderal), timolol (Blocadren), metoprolol (Lopressor, Toprol XL), pindolol All of the others are moderately lipophilic
22 Functions of beta-blockers Decrease palpitations during panic attacks Decrease essential tremors Decrease situational anxiety Decrease symptoms of PTSD Episodic dyscontrol syndrome Decrease HR in patients with Grave s disease Decrease portal pressure in patients with cirrhosis and esophageal varices Decrease migraine headaches by 50% in 50% of the patients (mechanism unknown) Preoperatively in cardiac patients undergoing noncardiac surgery
23 3 Classes of Calcium Channel Blockers 1) Verapamil (Isoptin SR, Verelan and Verelan PM, Calan and Calan SR, Apo-Verap, Novo-Veramil, Nu-Verap,) block calcium channels primarily on the coronary vessels and the AV node increasing blood flow to the heart and decreasing impulses through the AV node used to decrease workload of heart and slow the heart rate; HTN, angina, atrial fib 2) Calcium channels in bowels (elderly)
24 2) Diltiazem Cardizem, Dilacor XL dilates calcium channels on the coronary (1/5 affinity for coronary channels) and peripheral vessel calcium channels; Clinical uses Atrial fibrillation, Hypertension, Angina, Vasospasm Less constipation
25 3) DIPINES Peripheral vessel calcium channel blockers Amlodipine (Norvasc) Felodipine (Plendil)** Nifedipine (Procardia XL, Adalat) Nicardipine (Cardene) Isradipine (Dynacirc) Nisoldipine (Sular) Clevidipine (Cleviprex) for IV use MOA: Block the peripheral vascular calcium channels
26 Clinical uses of the dipines Hypertension Vasospasm Prinzmetal s angina, Raynaud s phenomenon, cocaine-induced vasospasms FYI: Ureteral spasm in patients with small kidney stones (try slow release nifedipine 30 mg qd x 5-7 days) male contraceptive
27 The Statin Sisters Who are they? lovastatin (Mevacor) simvastatin (Zocor)*--no more than 40 mg/d due to increased risk of rhabdomyolysis atorvastatin (Lipitor) fluvastatin (Lescol) pravastatin (Pravachol) rosuvastatin (Crestor) pitavastatin (Livalo)
28 The Statin Sisters what do they do? Inhibits the enzyme HMG-CoA reductase in the liver HMG-CoA reductase is responsible for the production of the bad guy LDL-cholesterol; works primarily at night to produce LDL, so the statins work the best when taken before bedtime (exception to the rule--atorvastatin) LDL is the most atherogenic of the cholesterol bunch and puts fat right smack dab into all of the arterial walls; therefore, statins decrease LDL-cholesterol Statins decrease CAD, PVD, CVD risk and increase survival rates Begin with a dose that drops the LDL-C by 30-40%
29 The Statin Sisters Reduce total cholesterol levels Decrease plaque formation Stabilize plaques and prevent plaque rupture Shrink plaques in all arteries (prevent stroke) Anti-inflammatory effects (other clinical uses?)
30 The afils 1998 and the Pfizer Riser (Viagra) Erectile dysfunction Prior to November 1998 What are the causes of ED? Athero, neuro, drugs, testo, psychological (the stamp test) Sildenafil (Viagra)(Revatio for pulmonary arterial hypertension) Vardenafil (Levitra) Tadalafil (Cialis)(Adcirca for PAH) the weekend warrior Boost nitric oxide potent vasodilator Can use in patients with stable CHD
31 Can t use with nitroglycerin When was your last dose of Viagra? Can t use Viagra or Levitra within 24 hours of receiving NTG; Cialis within 36 hours Side effects Hypotension Headaches GERD Blue vision Priapism A surprise side effect of the afils
32 Sexually transmitted diseases have increased by over 300% in the over 60 crowd since the release of Viagra More sex No pregnancy worries Swingin singles Who cares what the neighbors think? Swimming pools and golf courses Can you have a heart attack during sex? Only if
33 The dronates for osteoporosis The dronates for osteoporosis Alendronate [Fosavance] (Fosamax + D), clodronate [Ostac,Bonefos), Risendronate (Actonel), ibandronate (Boniva) zoledronic acid [Aclasta](Zometa)(Reclast) and pamidronate (Aredia)--cancer Trigger apoptosis of osteoclasts Osteoblasts continue to build bone matrix but without remodeling Any downside? Fractures? Negligible risk Osteonecrosis of jaw? Risk is highest with IV zolendronic acid and pamidronate for cancer Rx
34 The prazoles Proton Pump Inhibitors* Omeprazole (Prilosec)(first released as Losec in U.S.) Lansoprazole (Prevacid) Dexlansoprazole (Dexilant/Kapidex -old name) Rabeprazole (Aciphex) Pantoprazole (Protonix) Esomeprazole (Nexium)-- the purple pill *BIG Exception: Aripiprazole/Abilify an new antipsychotic a dopamine system stabilizer
35 The prazoles Proton Pump Inhibitors MOA Inhibition of the proton pump at the lumenal surface of the stomach especially after a meal PPIs work here H+, Intrinsic Factor-B12 Lumenal surface Parietal cell Basilar surface H2 receptors H2 H2 blockers work here
36 The prazoles Work within 4-7 days to reduce all acid in the stomach; take before the first meal of the day or before the dinner meal (especially if nocturnal GERD is a problem) Blocking acid production also decreases the release of intrinsic factor which is necessary for binding B12 Do you need B12? YES. Do you need acid to digest food? NO Do you need acid to zap food-borne pathogens? YES Do you need acid to absorb calcium? YES (use calcium citrate for low acid conditions elderly and PPI use) NO acid, no IRON
37 The antifungals--the azoles Miconazole (Monistat) Clotrimazole (Mycelex) Fluconazole (Diflucan) Itraconazole (Sporanox) Ketoconazole (Nizoral) Voriconazole (Vfend) Posaconazole (Noxafil) newest of the bunch (HIV) DRUG INTERACTIONS You have a yeast infection
38 The antiherpetics the cy{i}clovirs Acyclovir (Zovirax) Famciclovir (Famvir) Valacyclovir (Valtrex) Ganciclovir (Cytovene) CMV retinitis in HIV patients; CMV pneumonitis in transplant patients
39 The antiherpetics--vzv Acyclovir (Zovirax)(4000/d) Famciclovir (Famvir)(750/d) Valacyclovir (Valtrex)(3000/d) Ganciclovir (CMV retinitis) Tx must be started within hours after the first signs of a rash appear. +Prednisone Zostavax for prevention
40 The antibiotics the fluoroquinolones, the floxacins Ciprofloxacin (Cipro)*(2) ( INR) Lomefloxacin (Maxaquin)(2) Norfloxacin (Noroxin)*(2) Ofloxacin (Floxin)(2)* *uncomplicated UTI if resistance to TMP/SMX is 20% Levofloxacin (Levaquin) (3) too broad spectrum for UTI Gemifloxacin (Factive)(4) Moxifloxacin (Avelox)(4) effective against TB WARNINGS: C. difficile after the quinolones acute tendonitis in elderly and patients on corticosteroids
41 It s a MAB, MAB, MAB (monoclonal antibodies) world Infliximab (Remicade) targeted against TNF-α, the culprit in Crohn s disease, RA, psoriasis; TB testing prior to use Adalimumab (Humira) as above Trastuzumab (Herceptin) HER2-neu+ Breast cancers; when given in early stages, prognosis improves significantly Cetuximab (Erbitux) colon cancer (Martha Stewart) Bevacizumab (Avastin) inhibits angiogenesis; used to inhibit tumor growth; used to decrease neovascular growth in the retina; glioblastoma
42 THANK YOU and remember Never under any circumstances take a sleeping pill and a laxative on the same night. Barb Bancroft, RN, MSN, PNP BBancr9271@aol.com
43 Selected bibliography Bonakdar RA. Herb-drug interactions: what physicians need to know. Patient Care 2003; January: ) Cooper WO et al. Major congenital malformations after firsttrimester exposure to ACE inhibitors. N Engl J Med 2006 Jun 8; 354: Codario RA. Do we use an ACE, an ARB, or both? What clinical trials tell us. Patient Care 2005 (April); Cramer C et al. Use of statins and incidence of dementia and cognitive impairment without dementia in a cohort study. Neurology 2008; 71:344. Cayley WE. Are beta blockers effective first-line treatments for hypertension? Am Fam Phys 2007 Nov 1; 76(9); Evans RW. Migraine: A Question and Answer Review, Med Clin N Am 2009;
44 Bibliography Friedman JM. ACE inhibitors and congenital anomalies. N Engl J Med 2006 (June 8); 354:23. Gaynes BN, et al. The STAR*D Study: Treating depression in the real world, Cleveland Clinic Journal of Medicine 2008; 75 (1): Kramer JM et al. Comparative effectiveness of beta-blockers in elderly patients with heart failure. Arch Intern Med 2008 Dec 8; 168:2422 Nierenberg AA, et al. A Critical Overview of the Pharmacologic Management of Treatment-Resistant Depression, Psychiatric Clinics of North America 2007; 30(1): Tatro DS, ed. Drug Interaction Facts: Herbal supplements and Food. St. Louis, MO. A. Walters Kluwer Co; 2004; also available at
45 Bibliography Goh Sk, Yang KY, Koh JS, et al. Subtrochanteric insufficiency fractures in patients on alendronate therapy: a caution. J Bone Joint Surg BR 2007;89: Odvina CV, Zerwekh JE, Rao DS, Maalouif N, et al. Severely suppressed bone turnover; a potential complication of alendronate therapy. J Clin Endocrinol Metab 2005;90:
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